Antibody-directed enzyme prodrug therapy (ADEPT) delivers chemotherapeutic agents in high concentration to tumor tissue while minimizing systemic drug exposure. B-Lactamases are particularly useful enzymes for ADEPT systems due to their unique substrate specificity that allows the activation of a variety of lactam-based prodrugs with minimal interference from mammalian enzymes. We evaluated the amino acid sequence of B-lactamase from Enterobacter cloacae for the presence of human T-cell epitopes using a cell-based proliferation assay using samples from 65 community donors. We observed a low background response that is consistent with a lack of preexposure to this enzyme. B-Lactamase was found to contain four CD4 + T-cell epitopes. For two of these epitopes, we identified single amino acid changes that result in significantly reduced proliferative responses while retaining stability and activity of the enzyme. The B-lactamase variant containing both changes induces significantly less proliferation in human and mouse cell assays, and 5-fold lower levels of IgG1 in mice were observed after repeat administration of B-lactamase variant with adjuvant. The B-lactamase variant should be very suitable for the construction of ADEPT fusion proteins, as it combines high activity toward lactam prodrugs, high plasma stability, a monomeric architecture, and a relatively low risk of eliciting an immune response in patients. [Mol Cancer Ther 2005;4(11):1791-800]
Many youth who are incarcerated within juvenile correctional facilities experience mental health disorders, histories of victimization and suicide ideation. Strengths‐based intervention programmes are intended to enhance participants' resilience against such challenges. However, little is known about how the composition of intervention groups contributes to programmes' efficacy. This study addresses the impact of within‐group similarity on the success of a strengths‐based intervention for incarcerated young men (n = 141). Similarity was assessed in terms of self‐reported demographics and behaviours and belief systems. Youths' masculine ideology, caring and cooperative behaviours, ethnic pride and respect for differences, self‐efficacy regarding education and non‐violence, and attitudes about criminal behaviour were measured before and after intervention. Results indicate that participants' caring and cooperative behaviour increased during the intervention. However, their education‐related self‐efficacy was reduced, and the perceived benefits of criminal activity increased. These changes were moderated by group composition: less similarity between participants and their group members was associated with less negative change. In the context of juvenile corrections facilities, where staying the same may be a relatively positive outcome, perhaps the more relevant question is not which processes and characteristics of others better enable youth to change but which experiences help them retain positive aspects of themselves. Copyright © 2014 John Wiley & Sons, Ltd.
is also related to their own perpetration of IPV, specifically. However, existing research is yet to examine the extent to which men participating in batterer intervention programs (BIPs), a common form of treatment for perpetrators of IPV, receive messages about the perpetration of IPV from within their social networks, or whether or how BIP participants contribute to dialogues about abuse within their social networks.The purposes of the current study were to (1) describe the members of BIP
In recent decades, the use of strengths-based approaches has become increasingly popular in youth intervention and prevention programs (Maton et al., 2004), which emphasize creating emotionally safe environments through the process of relational community building (Maton, 2000). However, relatively little is known about the relationship between group composition, specifically similarity between group members, and emotional safety and program efficacy. This thesis examines the relationship between adolescent males' similarity to their peers in terms of their demographic profiles and behaviors and belief systems, experiences of emotional safety, and changing behaviors and belief systems in a strengths-based intervention program within Ohio juvenile correctional facilities. Results indicate that in the cases of education-related selfefficacy and the benefits associated with criminal activity, participants significantly changed in the direction opposite of the program's intentions. However, these negative changes were attenuated by differences between participants and their peers in the program. Theoretical implications and potential explanations are discussed.
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